We propose to study the role of deposition and clearance of aerosols in the airways of the human lung in the pathogenesis and treatment of chronic obstructive lung disease. A mathematical model of aerosol deposition-clearance will be further refined and the dose to each airway order calculated for instantaneous, intermittent, and continuous aerosol deposition. The model of instantaneous aerosol deposition will be tested by determining the deposition of radiotagged aerosols in large, mid, and peripheral airways in the human lung using a gamma camera. To aid in the interpretation of regional in vivo deposition patterns, "deposition" patterns will be constructed in a phantom of the thorax and the images obtained compared to the in vivo images. Mucociliary transport in the trachea, large and small airways will be measured in healthy subjects using a multidetector probe anterior to the trachea and a gamma camera posterior to the thorax. Images on the gamma camera will again be compared to patterns obtained from the chest phantom and transport rates for all airways derived by comparing regional retention curves of the mid and outer zones of the lung with those derived by using the mathematical model. Aspirin, a prostaglandin inhibitor can be predicted to decrease mucociliary transport in the human lung. This hypothesis will be tested in 12 healthy nonsmoking subjects. The changes in regional clearance due to aspirin will be analyzed in terms of transport rates in each of the airways by again modifying the computer model to fit the retention curves. To investigate the site of action on metaproterenol on mucus transport within the trachebronchial tree and to compare systemic administration of this drug with aerosol administration, each of 12 subjects will undergo three studies. Persons with Sjogren's disease have sparse secretions and increased lung infection and can therefore be predicted to have abnormal mucociliary transport. Regional mucociliary transport and the effect of metaproterenol on aiding the clearance of these secretions will be studied in 10 patients. The changes in regional deposition and clearance due to drugs and disease will be used to modify the model of deposition and clearance. In this way we hope to further elucidate the role of aerosol deposition and clearance in the pathogenesis of chronic obstructive lung disease.